mpi-0479605

MPI-0479605 is a potent and selective ATP competitive inhibitor of Mps1. Cells treated with MPI-0479605 undergo aberrant mitosis, resulting in aneuploidy and formation of micronuclei. In cells with wild-type p53, this promotes the induction of a postmitotic checkpoint characterized by the ATM- and RAD3-related-dependent activation of the p53-p21 pathway. In both wild-type and p53 mutant cells lines, there is a growth arrest and inhibition of DNA synthesis. Subsequently, cells undergo mitotic catastrophe and/or an apoptotic response. In xenograft models, MPI-0479605 inhibits tumor growth, suggesting that drugs targeting Mps1 may have utility as novel cancer therapeutics.

Product information

CAS Number: 1246529-32-7

Molecular Weight: 407.51

Formula: C22H29N7O

Synonym:

MPI-0479605

MPI 0479605

MPI0479605

Chemical Name: N6-cyclohexyl-N2-(2-methyl-4-morpholinophenyl)-9H-purine-2,6-diamine

Smiles: CC1=CC(=CC=C1NC1N=C2NC=NC2=C(NC2CCCCC2)N=1)N1CCOCC1

InChiKey: OVJBNYKNHXJGSA-UHFFFAOYSA-N

InChi: InChI=1S/C22H29N7O/c1-15-13-17(29-9-11-30-12-10-29)7-8-18(15)26-22-27-20-19(23-14-24-20)21(28-22)25-16-5-3-2-4-6-16/h7-8,13-14,16H,2-6,9-12H2,1H3,(H3,23,24,25,26,27,28)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

MPI-0479605 is a potent and selective ATP-competitive inhibitor of Mps1, with an IC50 of 1.8 nM. MPI-0479605 (0.1-10 μM) reduces cell viability of HCT-116 cells in a dose-dependent manner. MPI-0479605 shows severe defects in the ability to align chromosomes at the metaphase plate, but causes complete cytokinesis.

In Vivo:

MPI-0479605 (30 mg/kg daily or 150 mg/kg every fourth day (Q4D), i.p.) inhibits tumor growth by 49% and 74 % in HCT-116 xenografts. However, MPI-0479605 does not show inhibitory activity via daily dosing on the Colo-205 xenografts, and dosing every four days causes 63% tumor growth inhibition (TGI).

References:

1. Vijay Kumar D, Hoarau C, Bursavich M, Slattum P, Gerrish D, Yager K, Saunders M, Shenderovich M, Roth BL, McKinnon R, Chan A, Cimbora DM, Bradford C, Reeves L, Patton S, Papac DI, Williams BL, Carlson RO. Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors. Bioorg Med Chem Lett. 2012 Jul 1;22(13):4377-85. doi: 10.1016/j.bmcl.2012.04.131. Epub 2012 May 5. PubMed PMID: 22632936.
2. Tardif KD, Rogers A, Cassiano J, Roth BL, Cimbora DM, McKinnon R, Peterson A, Douce TB, Robinson R, Dorweiler I, Davis T, Hess MA, Ostanin K, Papac DI, Baichwal V, McAlexander I, Willardsen JA, Saunders M, Christophe H, Kumar DV, Wettstein DA, Carlson RO, Williams BL. Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1. Mol Cancer Ther. 2011 Dec;10(12):2267-75. doi: 10.1158/1535-7163.MCT-11-0453. Epub 2011 Oct 6. PubMed PMID: 21980130.

Products are for research use only. Not for human use.